Makoto Kaneda

Hokkaido University, Sapporo-shi, Hokkaido, Japan

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Publications (26)48.01 Total impact

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    ABSTRACT: Invasive fungal infection (IFI) causes morbidity and mortality among patients with hematological malignancies who receive cytotoxic chemotherapy or hematopoietic stem cell transplantation (HSCT). We evaluated the incidence and treatment outcomes of proven and probable IFI in 22 institutions between 2006 and 2008 following the recent European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) consensus criteria. We analyzed 2,821 patients with hematological malignancies, including 597 who had undergone HSCT; these included patients with acute leukemia (n = 697), myelodysplastic syndrome (n = 284), lymphoma (n = 1465), or multiple myeloma (n = 375). IFIs were diagnosed in 38 (1.3%) patients (18 proven and 20 probable), including 20 patients who underwent HSCT and 18 who received chemotherapy alone; these included patients with aspergillosis (n = 23), candidiasis (n = 6), mucormycosis (n = 6), trichosporonosis (n = 2), and geotrichosis (n = 1). The incidence of IFI was 5.4 % in allogeneic HSCT patients, 0.4 % in autologous HSCT patients, and 0.8 % in patients receiving chemotherapy alone. Eighteen patients with aspergillosis were diagnosed with probable pulmonary IFI as determined by computed tomography scan and positive galactomannan assay. Overall, antifungal targeted therapies resulted in successful outcomes in 60.0 % of patients. IFI-attributable mortality rate was higher in HSCT patients than in those receiving chemotherapy alone, but the difference was not statistically significant.
    International journal of hematology 10/2012; · 1.17 Impact Factor
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    ABSTRACT: Peripheral neuropathy is a well-known side effect of vincristine (VCR), a microtubule inhibitor commonly used to treat malignancies. Severe neurological adverse events can occur in patients with Charcot-Marie-Tooth disease (CMT) treated with VCR. Vindesine is also a microtubule inhibitor, which, like VCR, is widely used to treat malignancies. The case of an 11-year-old female patient with CMT type 1A who developed severe peripheral neuropathy induced by VCR given for her acute lymphoblastic leukemia is reported. Alternative treatment containing vindesine instead of VCR led to a successful outcome without a relapse of leukemia or neurological worsening of CMT.
    Journal of Pediatric Hematology/Oncology 01/2012; 34(3):239-41. · 0.97 Impact Factor
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    ABSTRACT: We report a 19-year-old patient with systemic-onset juvenile idiopathic arthritis (JIA) who developed a mediastinal germinoma during treatment with infliximab. Although the cancer risk of infliximab is controversial, this agent may have accelerated the growth of the germinoma. We conclude that the indications for tumor necrosis factor (TNF) inhibitors should be strictly decided and that a nationwide cohort study is necessary to assess the risk of cancer in patients with JIA exposed to biologics.
    Modern Rheumatology 11/2011; 22(4):621-4. · 1.72 Impact Factor
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    ABSTRACT: The rapidity of response to induction therapy is emerging as an important prognostic factor in children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Urine inorganic phosphate (IP) and uric acid (UA) may increase in patients with acute leukemia who undergo their induction chemotherapy, owing to the breakdown of tumor cells. The crystallization of UA or calcium phosphate in renal tubules can result in acute tumor lysis syndrome (ATLS). Some reports indicate that patients who experience ATLS have a better prognosis than those who do not. We investigated the relationship between urinary IP and UA excretion and treatment outcome in children with acute leukemia. Participants included 93 patients with ALL and 31 patients with AML. Urine samples were collected and measured for the first 3 days of induction chemotherapy. Among patients with ALL, urinary IP excretion was significantly higher in patients without relapse than in those with relapse and correlated with long-term outcome. Among patients with AML, urinary IP excretion was significantly higher in patients without induction failure (IF) than those with IF. We propose that higher urinary IP excretion could be a useful prognostic marker for determining favorable outcomes in patients with acute leukemia.
    Journal of Pediatric Hematology/Oncology 03/2011; 33(4):e143-8. · 0.97 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the efficacy and safety of piperacillin/tazobactam (PIP/TAZO) and cefozopran (CZOP) monotherapy in pediatric cancer patients with febrile neutropenia (FN). A total of 119 febrile episodes in 49 neutropenic pediatric cancer patients (20 females and 29 males) with a median age of 6.8 years (range, 0.3-18.4 years) received randomized treatment either with PIP/TAZO 125 mg/kg every 8 hr or CZOP 25 mg/kg every 6 hr. Clinical response was determined at completion of therapy. Durations of fever and neutropenia, the need for modification of the therapy, and mortality rates were compared between the two groups. The frequency of success without modification of treatment was not significantly different between PIP/TAZO (59.6%) and CZOP (53.2%). Durations of fever and antibiotic therapy did not differ between the treatment groups, and no major side effects were observed in either group. PIP/TAZO and CZOP monotherapy were both effective and safe for the initial empirical treatment of pediatric cancer patients with FN.
    Pediatric Blood & Cancer 03/2011; 57(7):1159-62. · 2.35 Impact Factor
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    ABSTRACT: We describe three males with X-linked SCID (X-SCID) who were successfully treated by reduced-intensity SCT from unrelated cord blood (CB). Mean age at transplant was 5.7 months (range, 3-9 months). Pre-transplant conditioning for all patients consisted of fludarabine (FLU) (30 mg/m(2) per day) from day -7 to day -2 (total dose 180 mg/m(2)) and BU 4 mg/kg per day from day -3 to day -2 (total dose 8 mg/kg). All CB units were serologically matched at HLA-A, B and DR loci. Although two patients had suffered from fungal or bacterial pneumonia before transplantation, there were no other infectious complications during transplantation. All patients engrafted and achieved 100% donor chimerism. We also confirmed full donor chimerism of both T and B cells. Only one patient developed acute GVHD grade III, which was resolved by increasing the dose of oral corticosteroid. None of the patients has developed chronic GVHD during follow up for 21-77 months. None of the patient received i.v. Ig replacement post transplant, or showed delay in psychomotor development. Reduced-intensity conditioning consisting of FLU and BU and transplantation from unrelated CB was an effective and safe treatment for these patients with X-SCID.
    Bone marrow transplantation 01/2011; 46(12):1526-31. · 3.00 Impact Factor
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    ABSTRACT: Hepatic veno-occlusive disease (VOD) is one of the most serious complications in stem cell transplantation (SCT). Although plasma protein C activity decreases in VOD after SCT, the timeframe of plasma protein C activity decreases during SCT is not known. We examined levels of plasma protein C serially during the course of SCT to determine the critical level and risk factors for VOD. Of 151 children who received SCT, 12 of them (7.9%) developed VOD. The mean minimum protein C activity in patients with VOD was significantly lower compared to that in patients without VOD (P < 0.0001). Receiver operating characteristic curve analysis revealed that the critical plasma protein C activity (cut-off point) for VOD was identified to be 34.5% with high sensitivity (100%) and specificity (83.3%), and the reduction of plasma protein C below the cut-off level (day +6.50 +/- 2.43) was observed mostly prior to the onset of VOD (day +7.33 +/- 2.64). The patients receiving melphalan in conditioning were found to be at high risk for VOD (P = 0.003). Among the melphalan containing regimens, melphalan + carboplatin + etoposide was a significant risk factor for depression of plasma protein C (P = 0.037). Plasma protein C level was a useful parameter of VOD after SCT, and activity below 34.5% was critical for VOD. The use of melphalan in conditioning causes a high risk for VOD.
    Pediatric Blood & Cancer 11/2009; 54(3):437-43. · 2.35 Impact Factor
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    ABSTRACT: To assess the incidence of and risk factors associated with postherpetic neuralgia (PHN) after hematopoietic cell transplantation (HCT) varicella zoster virus (VZV) infection, we conducted a retrospective chart review of 418 consecutive patients who underwent HCT between April 2005 and March 2007. The male/female ratio was 221/197, median age at HCT was 47 years (range: 0-69 years), and autologous/allogeneic/syngeneic HCT ratio was 154/263/1. Seventy-eight patients developed VZV infection after HCT. Sixty-two patients had localized zoster, 11 patients had disseminated zoster (rash like chicken pox), and 4 patients had visceral zoster. All cases were treated with acyclovir (ACV) or valacyclovir (VACV), and there was no VZV infection-related death. Twenty-seven (35%) of the 78 patients with VZV infection suffered PHN after resolution of VZV infection. Multivariate analysis showed that advanced age is the only risk factor in autologous HCT (P = .0075; odds ratio [OR] = 1.14; 95% confidence interval [CI], 0.97-1.33). On the other hand, advanced age (P = .0097; OR = 1.06; 95% CI, 1.01-1.12), male gender (P = .0055; OR = 12.7; 95% CI, 1.61-100.1), and graft-versus-host disease (GVHD) prophylaxis with a tacrolimus-based regimen (P = .0092; OR = 9.56; 95% CI, 1.44-63.3) were associated with increased risk of PHN in allogeneic HCT. This study for the first time clarified the risk of PHN in HCT recipients.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2009; 15(6):724-9. · 3.15 Impact Factor
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    ABSTRACT: The efficacy and safety of piperacillin/tazobactam plus ceftazidime (PIPC/TAZ+CAZ) versus sulbactam/ampicillin plus aztreonam (SBT/ABPC+AZT) as empirical therapy for febrile neutropenia were assessed in children with hematologic disease and solid tumor. A prospective randomized study was performed to evaluate the clinical response of 70 febrile episodes in the PIPC/TAZ+CAZ arm and 64 evaluable febrile episodes in the SBT/ABPC+AZT arm of the study. Clinical efficacy was evaluated at 120 hours, with treatment outcome criteria defined as follows. Success was defined as disappearance of fever, clinical improvement, eradication of the infecting organism, and maintenance of a response for at least 7 days after discontinuation of treatment. An infection was documented microbiologically in 14 episodes (20%) in the PIPC/TAZ+CAZ arm and in 8 episodes (13%) in the SBT/ABPC+AZT arm. The success rate was 57.1% in the PIPC/TAZ+CAZ arm and 62.5% in the SBT/ABPC+AZT arm (P>0.05). No major adverse effects were observed in the study. PIPC/TAZ+CAZ and SBT/ABPC+AZT are effective and safe for initial empirical treatment of febrile episodes in neutropenic pediatric patients. The clinical efficacy of SBT/ABPC+AZT is equivalent or superior to that of PIPC/TAZ+CAZ, the effect of which is already proven against febrile neutropenia. Therefore, SBT/ABPC+AZT may be a treatment of choice for febrile neutropenia in pediatric cancer patients.
    Journal of Pediatric Hematology/Oncology 04/2009; 31(4):270-3. · 0.97 Impact Factor
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    ABSTRACT: We examined the result of cord blood transplantation (CBT) for acute lymphoblastic leukemia (ALL) in children. Fifty ALL patients underwent stem cell transplantation in our hospital. Among these, 23 patients received related bone marrow transplantation and peripheral blood stem cell transplantation (R-BMT/PBSCT), 17 patients received unrelated bone marrow transplantation (U-BMT), and 10 patients received unrelated cord blood transplantation (U-CBT). The 5-year overall survival rates after R-BMT/PBSCT, U-BMT and U-CBT were 64.6%, 32.3%, and 85.7%, respectively. Event-free survivals after 5 years were 59.6%, 14.7%, and 70.0%, respectively. The relapse rate in the U-CBT group was equal to that in the R-BMT/PBSCT group, and the transplant-related mortality of U-CBT was 0%. Our data show that U-CBT should be the first choice for patients with refractory or relapsed ALL who have no related HLA-matched donor.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 01/2009; 49(12):1593-8.
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    ABSTRACT: Invasive fungal infections (IFI) are an important complication in hematologic malignancies and stem-cell transplantation (SCT). However, there are limited data characterizing IFI in children. The clinical feature of IFI after chemotherapy and SCT were analyzed in 334 pediatric patients treated at Hokkaido University Hospital from 1997 to 2006. The cumulative incidence of IFI was 6.9%; this comprised cases of proven, probable and possible IFI at rates of 1.2%, 3.0%, and 2.7%, respectively. The infected lesions were lung in 14 patients, liver in 5 patients, brain in 3 patients, fungemia in 2 patients, kidney in 1 patient, and endophthalmitis in 1 patient. The mortality of IFI was 48.2%, excluding patients who died due to relapse and interstitial pneumonitis; in particular, 71.4% patients with a lung lesion (10/14) died due to IFI. Fifty-nine pediatric patients died in our institution over the 10-year period of the study and IFI was the direct cause of death in 18.6% (11/59) of the patients. Risk factors for IFI with chemotherapy and SCT were also analyzed. Univariate analysis showed that age at diagnosis older than 10 years, relapse of original disease, long-term administration of broad-spectrum antibiotics, and acute myelogenous leukemia (AML) were the risk factors for IFI. All patients with IFI received long-term antibiotic therapy. AML was most strongly associated using a multivariate analysis. The prognosis of IFI has been expected poor; therefore, prevention of this condition, especially for older patients with AML, would be important.
    Journal of Pediatric Hematology/Oncology 01/2009; 30(12):886-90. · 0.97 Impact Factor
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    ABSTRACT: The aim of this randomized study was to evaluate the efficacy of cefozopran monotherapy and piperacillin-tazobactam plus ceftazidime (PIPC/TAZ + CAZ) combination therapy in pediatric neutropenic patients. A total of 51 patients with 138 episodes of febrile neutropenia received antibiotic therapy. Of these episodes, 95 were considered eligible for the study. The episodes were treated randomly with either piperacillin-tazobactam (125 mg/kg/day) plus ceftazidime (100 mg/kg/day) or with cefozopran (100 mg/kg/day). Success was defined as resolution of fever and clinical signs of infection within 120 hr following initiation of antibiotic therapy. Duration of neutropenia did not differ statistically between the two groups, and resolution of fever in all cases without complication was seen before recovery from severe neutropenia. The overall success rate was 61%. There was no statistically significant difference between the two groups: 53% for PIPC/TAZ + CAZ versus 69% for cefozopran (P = 0.122). Blood cultures were positive in eight episodes (8.4%), but there were not deaths as a result of infection. Both cefozopran and PIPC/TAZ + CAZ combination therapy are safe and well tolerated in pediatric neutropenic patients. Our results show that cefozopran is a good candidate for monotherapy for neutropenic fever.
    Pediatric Blood & Cancer 12/2008; 51(6):774-7. · 2.35 Impact Factor
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    ABSTRACT: Previously, we reported the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) as an underestimated complication associated with SCT. In the present report, we analyzed detailed data on a larger number of patients with SIADH following SCT and found different SIADH clinical features following cord blood SCT (CBSCT) and BMT/PBSCT. The median onset of SIADH following CBSCT and BMT/PBSCT was 19 and 46 days after SCT, respectively, and the median numbers of WBC at the onset of SIADH were 1.0 and 3.1 x 10(9)/l, respectively. Furthermore, severe symptoms such as seizures, somnolence and rigidity of limbs were observed only in patients with CBSCT (8/15 vs 0/10). These differences were statistically significant (P<0.01). Although the precise basis for SIADH following SCT still remains unknown, the different features of SIADH observed following CBSCT and BMT/PBSCT may provide important clues to the disease mechanism following SCT. Additionally, we confirmed our previous results that patients with SIADH showed a higher overall survival and event-free survival rates. However, we first suggested that they had some neurological disorders and that neurological sequelae such as developmental delay and seizures would consequently occur.
    Bone marrow transplantation 08/2008; 42(11):743-8. · 3.00 Impact Factor
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    ABSTRACT: We report 2 pediatric cases of cerebral fungal infection. A patient with severe aplastic anemia developed an Aspergillus species brain abscess and pulmonary aspergillosis after peripheral blood stem cell transplantation. Despite administration of micafungin, amphotericin B, and flucytosine, the patient died 2 months after the transplantation because of underlying pulmonary aspergillosis. Another patient with acute myelogenous leukemia developed a huge brain abscess with histopathologic findings suspicious of mucormycosis. This patient was cured with combination therapy of antifungal agents and intensive surgery, without sequelae. It is important to perform aggressive multimodality treatment, when indicated, including surgical intervention, even if in myelosuppression.
    Journal of Pediatric Hematology/Oncology 04/2008; 30(3):249-53. · 0.97 Impact Factor
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    ABSTRACT: The authors encountered a 7-year-old girl with a huge brain abscess and invasive pulmonary lesion due to fungus, who had been treated for acute myelogenous leukemia (AML). Although she was administered voriconazole to prevent fungal infection, she developed partial seizure and paralysis of the left side because of the huge brain abscess. Fungus culture and serum fungal markers, including Aspergillus antigen, were all negative. She underwent drainage and surgical resection of necrotic tissue after antifungal agents, including liposomal amphotericin B (L-AMB). Resection pathology revealed localized fungal infection, suspected as due to zygomycosis. The cerebral lesion reduced after the operation and the pulmonary lesion also vanished. We discontinued AML treatment because of the severe fungal infection; however, she has remained in continuous remission. Although Lipo-AMPH and itraconazole are comparatively effective for zygomycosis, progressive disseminated zygomycosis is extremely intractable. Our case underlines the feasibility and successful application of combined conventional antifungal agents and surgical resection in such a patient.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 01/2008; 48(12):1549-54.
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    ABSTRACT: Primary immunodeficiency diseases (PID) are rare but have a high associated risk of death from overwhelming infection in early childhood. Stem cell transplantation (SCT) can be curative for PID, but standardized protocols for each disease have not yet been established. Between May 1995 and May 2005, nine patients diagnosed with a PID received SCT at the Department of Pediatrics, Hokkaido University Hospital. The median age of the patients (eight boys and one girl) was 1.0 year (range: 6 months-4 years). Five patients had Wiskott-Aldrich syndrome (WAS), three had severe combined immunodeficiency (SCID), and one had X-linked hyper-IgM syndrome (X-HIGM). Four patients received bone marrow transplantation (BMT), and five received cord blood stem cell transplantation (CBSCT). All patients, including those with SCID, received a conditioning regimen: six (WAS and X-HIGM) received a myeloablative conditioning regimen, and three (SCID) received a reduced-intensity conditioning regimen. All the patients are alive and have stable, complete chimerism, based on a median follow-up period of 4 years. Moreover, all patients have good immune reconstitution, and none required immunoglobulin replacement therapy. Two patients had significant acute graft-versus-host disease (GVHD), and three patients had chronic GVHD. Four of the nine patients developed cytomegalovirus (CMV) infection after SCT. The transplantation procedures appear to have provided a permanent cure in nine PID patients. Early diagnosis and prompt performance of SCT with an optimal donor and conditioning regimen contributed to the favorable outcomes.
    Pediatrics International 01/2008; 49(6):795-800. · 0.88 Impact Factor
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    ABSTRACT: Invasive fungal infections (IFIs) are a significant cause of morbidity and mortality after stem cell transplantation (SCT). The incidence, outcome, and risk factors for IFI after allogeneic SCT were analyzed in 149 pediatric patients treated at Hokkaido University hospital from 1988 to 2006. The cumulative incidence of IFI after allogeneic SCT was 8.1%; this comprised cases of proven, probable, and possible IFI at rates of 0.7%, 4.0%, and 3.4%, respectively. Only 1 patient complicated with IFI in the 100 days after SCT, excluding cases with rejection. Antifungal drugs were effective in 3 of the 12 patients with IFI, but the other 9 patients died because of IFI and relapse of original diseases. Nonrelapse mortality was markedly higher for patients with IFI than for those without IFI (60.0% vs. 20.0%, P=0.0204). Univariate analysis showed that age at transplant, chronic graft-versus-host disease (GVHD), and a corticosteroid dose >2 mg/kg or 60 mg/d for 10 days or longer were possible risk factors for IFI. Of these factors, chronic GVHD was the only factor associated with IFI in a multivariate analysis. Treatment of IFI is very difficult and, therefore, prevention of this condition is important, especially upon occurrence of chronic GVHD.
    Journal of Pediatric Hematology/Oncology 11/2007; 29(11):786-91. · 0.97 Impact Factor
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    ABSTRACT: Hematopoietic SCT has improved the survival rates of patients with hematologic and metabolic disorders, as well as those with malignancy or immunodeficiency. Although various complications have been reported following allogeneic SCT, phimosis has rarely been reported, and the predisposing risk factors for phimosis have not been determined. In this study, the occurrence of severe phimosis following allogeneic SCT in boys was analyzed, and its risk factors were determined. The patients were under 15 years of age. Phimosis was observed in 32.6% of 46 patients after allogeneic SCT; 13.0% of cases required surgery. On univariate analysis, risk factors for severe phimosis included chronic GVHD and the use of a conditioning regimen including anti-thymocyte globulin (ATG). Multivariate analysis showed that chronic GVHD was an independent risk factor for severe phimosis. Thus, severe phimosis is an important complication of SCT in boys, especially in patients with chronic GVHD.
    Bone Marrow Transplantation 09/2007; 40(4):335-8. · 3.54 Impact Factor
  • British Journal of Dermatology 07/2007; 156(6):1373-4. · 3.76 Impact Factor
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    ABSTRACT: We describe an 8-year-old girl with chronic active Epstein-Barr virus (EBV) infection (CAEBV) who was treated successfully by reduced-intensity stem cell transplantation (RIST) from unrelated cord blood (CB). She had been suffering from fever, abdominal pain, and interstitial lymphadenopathy, and CAEBV was diagnosed. After chemotherapy that included etoposide, the amount of EBV decreased transiently below the detection level. However, the disease due to CAEBV worsened despite the chemotherapy, and she finally needed chemotherapy every week. Therefore, instead of conventional myeloablative transplantation, we performed CB transplantation with reduced-intensity conditioning regimens consisting of low-dose total body irradiation, fludarabine, and etoposide. CB, for which human leukocyte antigen (HLA) was 2-loci mismatched on the DR loci from an unrelated donor, was infused after conditioning. Although grade III acute graft-versus-host disease (GVHD) in the gut and chronic GVHD in the lung developed, the symptoms of GVHD disappeared with immunosuppressive therapy. After 15 months, the patient remained a complete chimera, with undetectable levels of EBV in peripheral blood and bone marrow. We conclude that RIST from unrelated CB can be indicated for some cases of CAEBV who are refractory to chemotherapy and have no HLA-matched related and unrelated donors as the source of bone marrow or peripheral blood stem cells.
    Journal of Pediatric Hematology/Oncology 05/2006; 28(4):254-6. · 0.97 Impact Factor

Publication Stats

164 Citations
48.01 Total Impact Points

Institutions

  • 2006–2012
    • Hokkaido University
      • Department of Pediatrics
      Sapporo-shi, Hokkaido, Japan
  • 2011
    • Hokkaido University Hospital
      • Division of Pediatrics
      Sapporo-shi, Hokkaido, Japan
  • 2008
    • Oji General Hospital
      Томакомай, Hokkaidō, Japan